Osteoporosis and obesity are major public health concerns. Recent estimates indicate that the US population consists of 25% obese, and, among the elderly, 50% of all osteoporotic individuals have age-associated osteoporosis, one of the most common and debilitating types of bone disease. Although the mechanisms involved remain poorly defined, recent studies suggest that age-associated osteoporosis is a stem cell disease. Human bone marrow mesenchymal stromal/stem cells (BMSCs) are multipotent stem cells that can differentiate into osteoblasts. MicroRNAs (miRNAs), a class of short single-stranded noncoding RNAs are post-transcriptional regulators that can modulate the homeostasis of multiple genes and associated pathways simultaneously. Changes in miRNA expression have been linked to the development of numerous disorders, including musculoskeletal disorders. While miRNAs are emerging as important modulators of cell function and phenotype development there remains a need to determine the role of miRNA and their downstream targets in human BMSCs differentiation or in the regulation of bone metabolism with aging.
Accordingly, it is an object of the invention to provide compositions and methods for altering the expression of miRNAs and downstream targets of miRNAs that are important for regulation of BMSC differentiation.
It is another object of the invention to provide compositions and methods for treating musculoskeletal disorders in a subject.